STREPTOKINASE-PLASMIN COMPLEX BINDS TO PLASMINOGEN RECEPTORS ON RAT HEPATOCYTES AND HUMAN ENDOTHELIUM

Streptokinase is a bacterial protein used in the treatment of thromboembolic disorders. In the circulation, streptokinase rapidly forms a complex with plasminogen which then functions as a plasmin gen activator. The processes involved in the clearance of streptokinase-plasmin complex (SkPl) from the vascular compartment in man remain unclear. The present study examined the interaction of SkPl with human umbilical vein endothelial cells (HUVECs) and rat hepatocytes. SkPl was formed with I-125-plasminogen and then inactivated with di-isopropylfluorophosphate. The DIP-SkPl bound to rat hepatocytes and to HUVECs at 4-degrees-C and 37-degrees-C. Lysine displaced greater than 70% of the bound DIP-SkPl. Comparable levels of I-125-DIP-SkPl displacement were obtained with non-radiolabelled DIP-SkPl and DIP-plasmin. When the DIP-SkPl was formed with I-125-streptokinase, binding to cellular receptors was unchanged; however, I-125-streptokinase, in the absence of plasminogen, did not bind to hepatocytes or HUVECs. At 37-degrees-C, there was no evidence for cellular uptake or degradation of bound DIP-SkPl. Hepatocytes and HUVECs treated with active SkPl demonstrated increased I-125-plasminogen binding capacity. After treatment with 0.5-mu-M SkPl for 1 h at 4-degrees-C, the increase in plasminogen binding to hepatocytes was approximately 7-fold; the increase in plasminogen binding to HUVECs was 2.4-fold. These studies demonstrate that SkPl binds to hepatocytes and HUVECs localising pro-fibrinolytic activity near the cell surface. The interaction of SkPl with cell-surface receptors may affect the plasma clearance of SkPl in man.